A Hormonal Remedy for Brain Injuries Is Explored

Late one evening last December, 18-year-old Michelle Vaquero was crossing a busy street in San Jose, Calif., when a car slammed into her. She landed more than 30 feet away. An ambulance rushed her to Santa Clara Valley Medical Center, where doctors diagnosed traumatic brain injury.

Miriam Richards, Ms. Vaquero’s mother, said that doctors at first offered little cause for optimism. “The impact was so severe that they didn’t give us any hope,” she said. “They didn’t tell us she’d be fine. They didn’t know how bad it was.”

Ms. Vaquero has been steadily recovering since the accident, and there is reason for Ms. Richards to hope that progress will continue. Shortly after she arrived at the hospital, Ms. Vaquero was enrolled in a study examining whether a surprising new treatment could minimize the damage to her brain: a three-day infusion of progesterone, the reproductive hormone.

The study, financed by the National Institutes of Health and overseen by Emory University in Atlanta, is designed to test the hypothesis that the hormone can reduce mortality and disability if administered right after a traumatic brain injury. Patients must begin the infusion within four hours of the injury, with outcomes assessed after six months. The study is one of two large trials of progesterone that have generated excitement among doctors because no medications have been approved for preventing the worst outcomes associated with serious brain injuries.

Dr. David Gordon, an assistant professor of neurosurgery at Montefiore Medical Center in the Bronx who is not involved in the research, said that he has “some measure of cautious optimism” about progesterone.

Moreover, patients with moderate traumatic brain injury who were given progesterone experienced greater functional improvement. A small study from China also reported positive outcomes with the hormone.

Traumatic brain injuries have received a lot of attention in the past decade for two reasons: the large number of such injuries suffered by soldiers in Iraq and Afghanistan, and the heightened focus on the risk of concussions in sports like football and hockey. According to the Centers for Disease Control and Prevention, about 1.7 million people a year experience a traumatic brain injury in the United States. Of those, 275,000 are hospitalized and more than 50,000 die. More than five million Americans are estimated to suffer from a long-term disability related to such injuries. The direct medical expenses and indirect costs, including lost productivity, have been estimated at $76 billion a year, according to the C.D.C.

The notion that progesterone might blunt the effects of brain injury originated with Donald Stein, a neuroscientist and a professor of emergency medicine at Emory. Decades ago, he noticed that female rats, especially those with the high levels of progesterone typical during pregnancy, were better than male rats at remembering certain tasks, like how to swim through a water maze after an induced brain injury.

Drug companies, however, were generally not interested in pursuing the research, which contradicted the longstanding belief that the brain cannot regenerate cells. Moreover, progesterone also had been widely regarded as a hormone involved solely in menstruation, embryogenesis and pregnancy.

“Although we think of it as a female hormone, there are a lot of clues in nature that this compound has multiple roles in the human body,” said Dr. David Wright, an associate professor of emergency medicine at Emory who collaborates with Dr. Stein and is lead investigator of the current clinical trial.

In fact, small amounts of progesterone are found in the brains of both women and men, suggesting that it has neuroprotective as well as reproductive functions.

Progesterone appears to affect multiple physiologic processes that follow an acute injury. It reduces the cerebral swelling that leads to brain cells dying off, for example. Progesterone also may blunt cellular damage from free radicals and promote myelin production in damaged nerve cells, experts believe.

The Emory trial will eventually include 1,140 participants at dozens of participating trauma centers around the country. Results are expected within three years, although a safety monitoring board will examine preliminary results this summer and could halt the study if the data suggest that the drug is highly effective.

A second large trial that includes international as well as domestic trauma sites is being conducted by BHR Pharma, which is using a different progesterone formulation from the one in the Emory trial. The Food and Drug Administration has promised to fast-track the approval process for the BHR formulation if the findings are positive.

(BHR Pharma has a licensing agreement with Emory related to the research. Dr. Stein, Dr. Wright and several other faculty members as well as Emory have received compensation arising from that agreement; Dr. Stein has also served as a paid consultant to the company.)

If the findings are positive, said Dr. James Quinn, a professor of emergency medicine at Stanford, which is also participating in the N.I.H. study, the potential benefits could extend to other serious conditions. “If this is neuroprotective for T.B.I., then how about for stroke?” he said. Ms. Vaquero and her doctors will not know until the trial is over whether she received progesterone or a placebo, but so far she is pleased with her recovery. After extensive physical therapy, she has recently relearned how to walk and hopes to continue her studies at San Jose City College.

“Sometimes there’s a couple of days in the month when I get depressed, but mostly I’m in a good mood,” she said. “I feel that I’ll be able to get back to normal, but it’s going to take time.”

A version of this article appears in print on June 19, 2012, on page D5 of the New York edition with the headline: An Hormonal Remedy for Brain Injuries Is Explored. Order Reprints|Today's Paper|Subscribe